نتایج جستجو برای: lrrk2 inhibitors

تعداد نتایج: 189958  

Journal: :BMB reports 2010
Wongi Seol

Parkinson's disease (PD) is the second most common neurodegenerative disease, and 5-10% of the PD cases are genetically inherited as familial PD (FPD). LRRK2 (leucine-rich repeat kinase 2) was first reported in 2004 as a gene corresponding to PARK8, an autosomal gene whose dominant mutations cause familial PD. LRRK2 contains both active kinase and GTPase domains as well as protein-protein inter...

2014
Joon Y. Boon Julien Dusonchet Chelsea Trengrove Benjamin Wolozin

LRRK2 is a protein that interacts with a plethora of signaling molecules, but the complexity of LRRK2 function presents a challenge for understanding the role of LRRK2 in the pathophysiology of Parkinson's disease (PD). Studies of LRRK2 using over-expression in transgenic mice have been disappointing, however, studies using invertebrate systems have yielded a much clearer picture, with clear ef...

Journal: :Neuro-degenerative diseases 2008
George Perry Xiongwei Zhu Asim K Babar Sandra L Siedlak Qiwei Yang Genta Ito Takeshi Iwatsubo Mark A Smith Shu G Chen

BACKGROUND Mutations in leucine-rich repeat kinase 2 (LRRK2) are thus far the most frequent genetic cause associated with autosomal dominant and idiopathic Parkinson's disease. OBJECTIVE To examine whether LRRK2 is directly associated with the pathological structures of Parkinson's disease, dementia with Lewy bodies, and other related disorders using highly specific antibodies to LRRK2. RES...

2017
James W. Jr. Maas Jing Yang Robert H. Edwards

Dominant mutations in leucine-rich repeat kinase 2 (LRRK2) produce the most common inherited form of Parkinson's disease (PD) but the function of LRRK2 remains poorly understood. The presynaptic role of multiple genes linked to PD including α-synuclein (α-syn) has suggested that LRRK2 may also influence neurotransmitter release, a possibility supported by recent work. However, the use of diseas...

2010
Udhaya Kumari Eng-King Tan

Mutations in Leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of sporadic and familial late onset Parkinson's disease (PD). The G2019S common mutation has been identified about 1% of sporadic cases and 4-7% of familial cases. Over 50 variants have since been identified in LRRK2, and at least 7 of these are confirmed to be pathogenic. In addition to pathogenic mutations, sever...

2015
Marta Garcia-Miralles Janaky Coomaraswamy Karina Häbig Martin C. Herzig Natalja Funk Frank Gillardon Martina Maisel Mathias Jucker Thomas Gasser Dagmar Galter Saskia Biskup

Mutations within the LRRK2 gene have been identified in Parkinson's disease (PD) patients and have been implicated in the dysfunction of several cellular pathways. Here, we explore how pathogenic mutations and the inhibition of LRRK2 kinase activity affect cytoskeleton dynamics in mouse and human cell systems. We generated and characterized a novel transgenic mouse model expressing physiologica...

2011
Hongxia Zhou Cao Huang Jianbin Tong Weimin C Hong Yong-Jian Liu Xu-Gang Xia

Parkinson's disease (PD) results from progressive degeneration of dopaminergic neurons. Most PD cases are sporadic, but some have pathogenic mutation in the individual genes. Mutation of the leucine-rich repeat kinase-2 (LRRK2) gene is associated with familial and sporadic PD, as exemplified by G2019S substitution. While constitutive expression of mutant LRRK2 in transgenic mice fails to induce...

2017
Kyung A. Han Lang Yoo Jee Y. Sung Sun A. Chung Ji W. Um Hyeyoung Kim Wongi Seol Kwang C. Chung

Leucine-rich repeat kinase 2 (LRRK2) is a Ser/Thr kinase having mixed lineage kinase-like and GTPase domains, controlling neurite outgrowth and neuronal cell death. Evidence suggests that LRRK2 is involved in innate immune response signaling, but the underlying mechanism is yet unknown. A novel protein inhibitor of phosphatase 3B, RCAN1, is known to positively regulate inflammatory signaling th...

Journal: :Molecular & cellular proteomics : MCP 2011
Andrea Meixner Karsten Boldt Marleen Van Troys Manor Askenazi Christian J Gloeckner Matthias Bauer Jarrod A Marto Christophe Ampe Norbert Kinkl Marius Ueffing

Mutations in human leucine-rich repeat kinase 2 (Lrrk2), a protein of yet unknown function, are linked to Parkinson's disease caused by degeneration of midbrain dopaminergic neurons. The protein comprises several domains including a GTPase and a kinase domain both affected by several pathogenic mutations. To elucidate the molecular interaction network of endogenous Lrrk2 under stoichiometric co...

Journal: :The Biochemical journal 2010
Iakov N Rudenko Mark R Cookson

Mutations in LRRK2 (leucine-rich repeat kinase 2) are the most common cause of familial PD (Parkinson's disease). Mutations that cause PD are found in either the GTPase or kinase domains of LRRK2 or an intervening sequence called the COR [C-terminus of ROC (Ras of complex proteins)] domain. As well as the two catalytic domains, LRRK2 possesses several protein-protein interaction domains, but th...

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